Most genome-wide significant risk variants (except rs1229984 and rs2066702) identified by GWASs are typically located in non-coding regions (Table 1), without clear effects on protein structure. Non-coding genetic variants can have effects on the function of proximate genes by altering the transcription, splicing or stability of the mRNAs or ncRNAs. Recent evidence suggests that LncRNAs are involved in a wide variety of cellular functions, including epigenetic silencing, transcriptional regulation, RNA processing, RNA modification (44–46), and implied in plasticity in the nervous system (47), neuropathological process (48), neurotransmission (49), and stress response (47). Dysregulation of many LncRNAs has been found to contribute to substance use disorders including alcohol, nicotine, heroin and cocaine dependence. For example, NEAT2, an LncRNA regulating synapse formation (50), was up-regulated in human brains of alcoholics (51); NEAT2, NEAT1, MIAT and MEG3 were up-regulated in human brains (NAc) of heroin abusers (52); and NEAT2, MIAT, MEG3 and EMX2OS were elevated in the NAc of cocaine abusers (52); smokers had dramatically elevated H19 expression in airway epithelium (53); demethylation of H19 was correlated to chronic alcohol use in males
